pH Dependence of the Inwardly Rectifying Potassium Channel, Kir5.1, and Localization in Renal Tubular Epithelia

Tucker, Stephen J.; Imbrici, Paola; Salvatore, Lorena; D’Adamo, Maria Cristina; Pessia, Mauro

doi:10.1074/jbc.c000127200

Cited by 116 publications

(139 citation statements)

References 16 publications

(17 reference statements)

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“…In some experiments we also examined the renal expression of Kir4.1 and Kir5.1 for comparison (1,2,32).…”

Section: Biochemical Characterization Of Brain Kir41 Andmentioning

confidence: 99%

“…The two Kir channels distributed differentially within a Mü ller cell. They also have different biophysical properties and intracellular pH (pH i ) dependence (1,2,19). It is, therefore, suggested that the two Kir channels play distinct functional roles in the buffering of K ϩ ; the homomeric Kir4.1 localized at end feet facing the vitreous surface and at processes wrapping blood vessels may allow K ϩ extrusion, whereas heteromeric Kir4.1/5.1 channels at processes surrounding neurons may be responsible for pH idependent K ϩ uptake.…”

mentioning

confidence: 99%

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Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

Hibino

Fujita

Iwai

et al. 2004

Journal of Biological Chemistry

147

142

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“…In some experiments we also examined the renal expression of Kir4.1 and Kir5.1 for comparison (1,2,32).…”

Section: Biochemical Characterization Of Brain Kir41 Andmentioning

confidence: 99%

mentioning

confidence: 99%

Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

Hibino

Fujita

Iwai

et al. 2004

Journal of Biological Chemistry

147

142

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“…It has been localized to the basolateral membrane of CCD principal cells with immunogold labeling (25) but has a Rb ϩ conductance almost 10ϫ greater than that for K ϩ (38), a property quite distinct from the basolateral K ϩ conductance. Members of the Kir4 subfamily of inward rectifiers, Kir4.1 and Kir4.2, along with heteromultimeric channels formed by these channels in combination with Kir5.1 (43,46), share several features of the basolateral principal cell K ϩ conductance. These channels have weak-to-moderate inward rectification with single-channel conductances in symmetric K ϩ of 20 -27 (31,(41)(42)(43)56), 25 (30), and 30 -60 pS (43) for Kir4.1, Kir4.2, and Kir4.1/5.1, respectively.…”

Section: Principal Cells Of Rat Ccd Have a Large Whole Cell K ϩmentioning

confidence: 99%

Basolateral K⁺conductance in principal cells of rat CCD

Gray

Frindt

Zhang

et al. 2005

American Journal of Physiology-Renal Physiology

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Whole cell K ϩ current was measured by forming seals on the luminal membrane of principal cells in split-open rat cortical collecting ducts. The mean inward, Ba 2ϩ -sensitive conductance, with 40 mM extracellular K ϩ , was 76 Ϯ 12 and 141 Ϯ 22 nS/cell for animals on control and high-K ϩ diets, respectively. The apical contribution to this was estimated to be 3 and 16 nS/cell on control and high-K ϩ diets, respectively. To isolate the basolateral component of whole cell current, we blocked ROMK channels with either tertiapin-Q or intracellular acidification to pH 6.6. The current was weakly inward rectifying when bath K ϩ was Ն40 mM but became more strongly rectified when bath K ϩ was lowered into the physiological range. Including 1 mM spermine in the pipette moderately increased rectification, but most of the outward current remained. The K ϩ current did not require intracellular Ca 2ϩ and was not inhibited by 3 mM ATP in the pipette. The negative log of the acidic dissociation constant (pKa) was ϳ6. homeostasis by setting the resting potential of the cell. K ϩ flux across the basolateral membrane can be in either direction depending on the physiological setting (22,33). In states where K ϩ conservation is required, for example on a low-K ϩ diet or during neonatal growth, K ϩ entering the cell by the active Na ϩ -K ϩ -ATPase is recycled across the basolateral membrane to prevent losses through apical K ϩ channels. In states of K ϩ excess or in the setting of increased aldosterone, the direction of net K ϩ flux across the basolateral membrane reverses (22, 33) such that K ϩ now enters the cell through the basolateral channels and is then secreted into the urine across the apical membrane. Finally, the basolateral K ϩ conductance influences Na ϩ reabsorption by helping to establish the apical membrane potential.Despite its importance, our knowledge of the molecular determinants that underlie the basolateral K ϩ conductance in principal cells is limited. From perfusion studies of isolated rat CCDs, it has been shown that the basolateral K ϩ conductance is Ba 2ϩ sensitive but TEA insensitive (35) and that the fractional apical resistance with amiloride in the lumen is 0.9 (36). The permeability sequence is K ϩ Ͼ Rb ϩ Ͼ NH 4 ϩ (35). Singlechannel recordings from K ϩ channels on the basolateral membrane are technically challenging as the basement membrane presents a barrier to formation of giga-ohm seals on the basolateral surface of these cells. Two approaches have been used to circumvent this problem: enzymatic digestion of the basement membrane (11) and mechanical removal of the adjacent intercalated cells permitting access to the lateral principal cell membrane (50). After collagenase digestion of the basement membrane, a 148-pS channel (cell attached) that decreased to 85 pS when excised into a low-K ϩ bath and a 67-pS channel (cell attached) that decreased to 28 pS when excised were observed (12). The larger conductance channel was inhibited by intracellular acidification with a negative log of the acidic disso...

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“…5A). These channels have in common that they are gated by intracellular protons (3)(4)(5)(6)26). We chose Kir1.1 to study the role of the position Ile-63 that corresponds to Arg-54 in Kir6.2.…”

Section: Arg-54 In the N Terminus Of Kir62 Is A Major Determinant Fomentioning

confidence: 99%

Phosphatidylinositol 4,5-Bisphosphate (PIP2) Modulation of ATP and pH Sensitivity in Kir Channels

Schulze¹,

Krauter²,

Fritzenschaft

et al. 2003

Journal of Biological Chemistry

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Phosphatidylinositol polyphosphates (PIPs) are potent modulators of Kir channels. Previous studies have implicated basic residues in the C terminus of Kir6.2 channels as interaction sites for the PIPs. Here we examined the role of the N terminus and identified an arginine (Arg-54) as a major determinant for PIP 2 modulation of ATP sensitivity in K ATP channels. Mutation of Arg-54 to the neutral glutamine (R54Q) and, in particular, to the negatively charged glutamate (R54E) impaired PIP 2 modulation of ATP inhibition, while mutation to lysine (R54K) had no effect. These data suggest that electrostatic interactions between PIP 2 and Arg-54 are an essential step for the modulation of ATP sensitivity. This N-terminal PIP 2 site is highly conserved in Kir channels with the exception of the pH-gated channels Kir1.1, Kir4.1, and Kir5.1 that contain a neutral residue at the corresponding positions. Introduction of an arginine at this position in Kir1.1 channels rendered the N-terminal PIP 2 site functional largely increasing the PIP 2 affinity. Moreover, Kir1.1 channels lose the ability to respond to physiological changes of the intracellular pH. These results explain the need of a silent N-terminal PIP 2 site in pH-gated channels and highlight the N terminus as an important region for PIP 2 modulation of Kir channel gating.Kir channels are a superfamily of eukaryotic channel proteins that are expressed in many tissues and responsible for important physiological processes such as cell excitability, insulin secretion, K ϩ homeostasis, vascular tone, and regulation of the heart rate. Four subunits assemble to a channel. Each subunit contains two transmembrane segments with cytoplasmic N-and C-terminal domains and a connecting loop forming the pore (1). Some members of the Kir channel family are endowed with gating mechanisms such as ATP gating (K ATP channels) (2) and pH gating (Kir1.1 and Kir4.1 channels) (3). These gating mechanisms are central for the diverse functions of Kir channels in physiology and the understanding of the related pathophysiology. Kir1, Kir4, and Kir5 channels, that are predominantly expressed in epithelia, are exquisitely sensitive to changes in intracellular pH in the physiological range (3-5). This pH sensitivity is mediated by the protonation of a lysine in the N terminus (Lys-80 in Kir1.1) that induces closure of the channel's pore by an allosteric mechanism (pH gating) (3, 6). Even small changes in the pH sensitivity can cause severe kidney defects such as the Bartter syndrome (3), highlighting the physiological importance of proper pH gating in Kir1.1 channels. Kir6 channels display a very ubiquitous expression pattern and, in coassembly with the sulfonylurea receptor (SUR), 1 represent the ATP-sensitive K ϩ channels (K ATP channels) (7). Intracellular ATP closes K ATP channels by binding to the Kir6.2 subunits (ATP gating), whereas the SURs act as regulatory subunits endowing the channel with sensitivity to MgADP and pharmacological compounds. The ATP/ADP dependence of K ATP channels couple...

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pH Dependence of the Inwardly Rectifying Potassium Channel, Kir5.1, and Localization in Renal Tubular Epithelia

Cited by 116 publications

References 16 publications

Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

Basolateral K⁺conductance in principal cells of rat CCD

Phosphatidylinositol 4,5-Bisphosphate (PIP2) Modulation of ATP and pH Sensitivity in Kir Channels

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pH Dependence of the Inwardly Rectifying Potassium Channel, Kir5.1, and Localization in Renal Tubular Epithelia

Cited by 116 publications

References 16 publications

Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

Basolateral K+conductance in principal cells of rat CCD

Phosphatidylinositol 4,5-Bisphosphate (PIP2) Modulation of ATP and pH Sensitivity in Kir Channels

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Basolateral K⁺conductance in principal cells of rat CCD